The construction of a means to overcome cancerous multidrug resistance by mediating the post-translational regulators of drug-efflux transporters

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590667
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: OGIHARA Takuo 高崎健康福祉大学, 薬学部, 教授 (80448886)
• Co-Investigator(Kenkyū-buntansha): KAORI Morimoto 高崎健康福祉大学, 薬学部, 講師 (90401009) ; MASAHIRO Kajita 高崎健康福祉大学, 薬学部, 准教授 (40591871) ; YOKO Idota 高崎健康福祉大学, 薬学部, 研究員 (90629594) ; KENTARO Yano 高崎健康福祉大学, 薬学部, 助手 (40644290)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: P-糖タンパク / がん多剤耐性 / 裏打ちタンパク / 膜上発現 / 調節因子 / ＥＲＭタンパク / 組織選択性

Outline of Final Research Achievements

P-glycoprotein (P-gp) excretes many therapeutic drugs from the cytoplasm to outside the cells. Therefore, it is well known as a major factor in multidrug resistance of cancer cells. Our previous study demonstrated that radixin among ezrin, radixin and moesin (ERM proteins) regulated P-gp transport activity and membrane localization. In this study, we investigated the relationship between P-gp and ERM proteins in cancer cells from other organs. The transport activity of intestinal P-gp was regulated by radixin in both normal and cancer cells. On the other hand, it was suggested that none of the ERM proteins affected the renal P-gp in either normal or cancer cells. Thus, we hypothesize that the functional regulation mechanism of P-gp via ERM proteins varies between different organs, such as the intestine and kidney, but not between normal and cancer cells in the same organ.

Free Research Field

生物薬剤学